GSK-3β通路在异丙酚预处理保护大鼠肝缺血再灌注损伤中的作用机制  

Role of GSK-3β in the protective effect of propofol pretreatment against hepatic ischemia-reperfusion injury and oxidative stress in rats

作　　者：曹懿[1] 段娜[2] 朱宇麟[2] 申新[2] 王强[2] 赵鸽[2] 

机构地区：[1]复旦大学附属闵行医院妇产科,上海201100 [2]西安交通大学第一附属医院麻醉科

出　　处：《中华肝胆外科杂志》2016年第10期692-696,共5页Chinese Journal of Hepatobiliary Surgery

基　　金：陕西省科学技术研究发展计划项目（2014K11-03-03-08）

摘　　要：目的探讨异丙酚预处理对大鼠肝缺血再灌注后氧化应激的影响及GSK-3β的作用机制。方法sD大鼠60只，随机分为4组：假手术组（s组）、缺血再灌注组（I-R组）、异丙酚预处理组（P组）、TDZDl8（GSK-3β抑制剂）预处理组（T组）。采用Nauta大鼠肝热缺血再灌注模型。分别在热缺血后30、60、90min开放动脉夹，再灌注120min。各实验组于再灌注末处死大鼠，抽取肝上下腔静脉血，测定血清ALT、AST、乳酸脱氢酶（LDH）；采集肝脏缺血组织观察肝脏组织形态学变化，检测丙二醛（MDA）和超氧化物歧化酶（SOD）。蛋白印迹法检测肝组织GSK-3pSer9、p-GSK-3pSer9蛋白表达。结果与s组比较，I—R组ALT、AST、LDH、MDA明显升高，SOD明显降低，p-GSK-3BSer9蛋白水平明显降低，肝组织HE染色显示肝细胞损伤明显，广泛肝细胞变性坏死，部分肝组织结构破坏不完整；与I—R组比较，P组和T组ALT、AST、LDH、MDA明显降低，SOD明显增高，p-GSK-3BSer9蛋白水平明显升高，肝组织HE染色显示肝细胞坏死减轻，肝组织结构破坏减轻。各组GSK-3BSer9表达没有明显的变化。结论异丙酚预处理能清除氧自由基，增强抗氧化能力，抑制脂质过氧化反应而减轻肝脏缺血再灌注损伤。异丙酚的这种保护作用是通过抑制GSK-3β活化，增强磷酸化GSK-3pSer9实现的。Objective To investigate the protective effect of propofol pretreatment against hepatic ischemia-reperfusion injury and oxidative stress in rats and the mechanism of the role of GSK-3β. Methods Sixty SD rats were randomly divided into four groups： sham operation group （S group） , ischemia-reperfu- sion group （I-R group）, propofol pretreatment group （P group）, TDZD-8 pretreatment group （T group）. The hepatic ischemia-reperfusion ral models were established by the method of Nauta. Rats were subjected to 30-min, 60-min and 90-min 70% warm ischemia of liver followed by reperfusion for 120 min, respectively. Propofol （ 12 mg/kg h） was injected via femoral vein 30 rain before ischemia till the end of reperfusion in P group and TDZD-8 （ 1 mg/kg） were injected via femoral vein 20 rain before ischemia in T group. The an- imals were killed at 120 min after reperfusion. Blood samples and the liver tissue were obtained. The levels of alanine aminotransferase （ ALT）, aspartate aminotransferase （ AST）, lactate dehydrogenase （ LDH）, ma- londialdehyde （MDA） and superoxide dismutase （SOD） were analyzed. Liver morphological changes were observed using optical microscopy, p-GSK-3β Ser9 and total GSK-313 expression was determined by Western blot. Results Compared with S group, AST, ALT, LDH and MDA level was increased, SOD level was re- duced, and p-GSK-3β Ser9 expression was significantly reduced in I-R group. Compared with I-R group, the content of AST, ALT, LDH and MDA was reduced significantly, SOD increased significantly, and the con- tent of p-GSK-3β Ser9 increased significantly in P group and T group. There were no significant differences between P group and T group. The hematoxylin-eosin staining of hepatic tissues revealed in I-R group had severe structural damage and periportal inflammatory cells infiltrated, hepatocyte necrosis and sinusoidal con- gestion. In P group and T group, liver tissues had normal structure, less cell death, edema and inflanunatoly cell infiltrati

关 键 词：异丙酚 氧化应激 肝脏 缺血再灌注损伤 大鼠 

分 类 号：R614[医药卫生—麻醉学]